Two-In-One Punch Knocks Out Drug Resistant Cancer Cells

November 4th, 2009 in Nanotechnology / Bio & Medicine

(PhysOrg.com) -- Cancer cells, like bacteria, can develop resistance to drug therapy, leading to relapse of disease. One approach showing promise in overcoming multidrug resistance in tumors is to combine two different anticancer agents in one nanoscale construct, providing a one-two punch that can prove lethal to such resistant cells. An example of this approach appears in the journal Small.

Huixin He and Tamara Minko led a team of investigators from academia and industry that used porous silica nanoparticles to deliver to cancer cells a traditional anticancer drug together with a therapeutic small interfering RNA (siRNA) molecule. Doxorubicin, the anticancer drug, kills tumors by triggering a form of cell death known as apoptosis, while the siRNA the researchers used suppresses the production of the protein Bcl-2, which malignant cells produce to stop apoptosis.

To create this two-for-one therapeutic, the investigators first load doxorubicin into the pores of silica nanoparticles and then coat the nanoparticle with spherical polymer nanoparticles known as dendrimers. The dendrimer-coated nanoparticles bind tightly to siRNA molecules, creating the novel therapeutic. When administered to multidrug resistance ovarian cancer cells, the nanoparticle formulation was over 130 times more lethal to the cells than was free doxorubicin. Most of this increase in anticancer activity resulted from the effects of the siRNA therapy.

The researchers noted, however, that since the nanoparticle uptake appears to be endocytosis mediated, and the doxorubicin delivered into the nucleus and perinuclear region of the cell, it is likely that this therapeutic approach is also able to bypass the pump mechanism cancer cells use to remove drugs that enter the cell via diffusion pathways. The researchers also found that the nanoparticles release very little of their doxorubicin payload outside of the cells, suggesting that the nanoparticle-based therapy might reduce the side effects associated with doxorubicin treatment.

This work, which was supported in part by the National Cancer Institute, is detailed in a paper titled, "Co-delivery of Doxorubicin and Bcl-2 siRNA by Mesoporous Silica Nanoparticles Enhances the Efficacy of Chemotherapy in Multidrug-Resistant Cancer Cells." Investigators from Carl Zeiss SMT and Merck & Co. also participated in this study.